Pargluva at EMDAC today
I have to apologize for not summarizing the key issues that the EMDAC will face during today’s discussions of Pargluva (muraglitazar) last night, but I was consumed by other matters yesterday. Suffice to say that FDA has had an opportunity to amass a very large volume of preclinical and clinical data on PPAR modulators, including PPAR alpha/gamma dual agonists (Pargluva’s mechanism). They know very well the issues of potential clinical concern. What they need from this committee is an outside view of potential concerns that have not been discussed in public forums like this previously. The cardiovascular issues, for instance (PPAR gamma-mediated phenomena), were publicly discussed during the approvals of troglitazone, rosiglitazone, and pioglitazone. Likewise, certain malignancy risks and the hepatotoxicity potential, have received public scrutiny. FDA will surely want to differentiate preclinical malignancy signals seen with the alpha/gamma agonists from those seen with the TZDs mentioned above and others that have not been approved to determine whether risk management should be different for this class. Although I haven’t read through the briefing docs yet, my personal experience with these classes of drugs makes me think that the advisory committee will endorse approval with currently available data and suggest (if not already suggested by BMS/Merck) that the sponsors perform active surveillance for malignancy in the postmarketing phase. They will also want to see a cardiovascular safety/efficacy study with hard outcomes performed (akin to what is curently being done for rosi- and pioglitazone).
